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S u s ta i n e d i n t e n s i v e t r a n s m i ss i o n o f Q f e v e r i n t h e s o u t h o f t h e N e t h e r l a n d s , 2 0 0 9

B Schimmer ([email protected])1, F Dijkstra1, P Vellema2, P M Schneeberger3, V Hackert4, R ter Schegget5, C Wijkmans6, Y van Duynhoven1, W van der Hoek1 1. Centre for Infectious Disease Control, (CIb), National Institute for Public Health and the Environment, RIVM, Bilthoven, the 2. Animal Health Service (GD), Deventer, the Netherlands 3. Jeroen Bosch Hospital, ’s Hertogenbosch, The Netherlands 4. Municipal Health Service South , Sittard-Geleen, the Netherlands 5. Municipal Health Service Brabant-Southeast, Helmond, the Netherlands 6. Municipal Health Service “Hart voor Brabant”, ’s Hertogenbosch, the Netherlands

The Netherlands is again facing a sharp increase in Q fever to the notification criteria. Notification of probable cases, defined notifications, after the unprecedented outbreaks of 2007 and 2008. as clinical signs with a single high antibody titre is voluntary. The most affected province of Noord Brabant has a high density of large dairy goat farms, and farms with abortion waves have Current situation been incriminated. Mandatory vaccination of small ruminants has From April 2009, a sharp increase in Q fever was observed again, started and should have an effect in 2010. A large multidisciplinary and a total of 345 cases (including 13 probable) were notified research portfolio is expected to generate better knowledge about between 1 January and 11 May 2009 (Figure 1). For 11 cases, transmission and additional control measures. the date of illness onset was in 2008 and one case fell ill in 2007, resulting in a total of 333 cases with confirmed or presumed illness Introduction onset in 2009. The overall male-to-female ratio for these 333 cases Q fever is a zoonosis caused by the obligate intracellular was 1.7:1 with a median age of 49 years (IQR 38-61 years). bacterium Coxiella burnetii. Cattle, sheep and goats are the primary animal reservoir, but the causative agent has also been The epidemic curve for 2009 shows an even steeper increase noted in many other animal species. Infected goats and sheep may in case numbers in April-May, than in the previous two years, abort, mainly in late pregnancy. The bacterium is shed in urine, suggesting that an epidemic of at least the same magnitude as faeces, milk and in especially high concentrations in placentas the one in 2008 is imminent. While most cases reside in the same and birth fluids of infected animals. Bacteria are transmitted to region in the province of Noord-Brabant as the cases reported in humans mainly through the aerosol route, resulting in subclinical 2007 and 2008 (see map in reference 3), the geographic area infection, a flu-like syndrome with abrupt onset of fever, pneumonia seems to be expanding (Figure 2). or hepatitis, after an incubation period of two to three weeks [1]. People with underlying conditions, especially heart valve lesions, Clinical features and diagnostics are more susceptible to developing chronic Q fever. Endocarditis, Pneumonia is the predominant clinical presentation of the the most common form of chronic Q fever is estimated to occur in Q fever cases in the Netherlands. For those patients notified in about 1% of acute Q fever cases. 2008 for whom clinical details were available, 545 presented with pneumonia, 33 with hepatitis, and 115 with other febrile illness Since 1978, when Q fever in humans became a notifiable (data not yet analysed in detail). Of the 226 cases in 2009 where disease in the Netherlands, until 2006, the number of notifications data regarding hospitalisation were available, 59 (26%) had been had ranged between 1 and 32 cases annually, with an average admitted to a hospital, a percentage comparable to figures in 2008, of 17 cases per year [2]. However, in 2007, Q fever emerged as but lower than the proportion of patients hospitalised in 2007 an important human and veterinary public health challenge with (49%). Clinical follow-up of patients that were diagnosed with acute large epidemics in the southern part of the Netherlands [3]. In Q fever in 2007, shows that Q fever is not always a mild disease 2007, 168 human cases were notified and in 2008 exactly 1,000 of short duration, as many cases still suffered from persisting human cases were registered (Figure 1). Notification criteria for fatigue several months after disease onset [4]. We have no clear acute Q fever are a clinical presentation with at least fever, or information about the occurrence of other chronic sequelae, such pneumonia, or hepatitis and confirmation of the diagnosis in the as endocarditis at this stage. laboratory. Currently, the laboratory criteria are a fourfold rise in IgG antibody titre against C. burnetii in paired sera or the presence The medical microbiology laboratories in the affected region of IgM-antibodies against phase II antigen. Identification of have jointly formulated diagnostic recommendations. Cases are C. burnetii in patient material with a PCR test will soon be added currently diagnosed with immunofluorescence assays (Focus

EUROSURVEILLANCE Vol. 14 · Issue 19 · 14 May 2009 · www.eurosurveillance.org 1 Diagnostics), in-house complement fixation tests or ELISA. Real- In March 2009, the Animal Health Service reported a Q fever- time polymerase chain reaction (PCR) tests were developed by positive farm in the province of Limburg with more than a thousand eight medical microbiology laboratories and the most sensitive goats. The place also serves as a care farm for young people (98%) PCR has been selected and has proven a valuable additional with mental disabilities who work there as part-time farmhands. tool for early diagnosis of acute Q fever in the time window before Prompted by this notification, the municipal health service (MHS) seroconversion. South Limburg performed active laboratory screening by ELISA of the individuals affiliated to this goat farm. The screening, Increased alertness of general practitioners together with easy which involved a total of 96 people, has resulted in 28 notified availability of diagnostic services certainly has an impact on the symptomatic cases to date. number of notifications. The current epidemic curve based on week of notification reflects a more real time situation than in previous Veterinary situation years, as the interval between date of illness onset and date of The total number of registered small ruminant farms in the diagnosis has decreased from a median of 77 days in 2007 (IQR Netherlands is 52,000, of which 350 are professional dairy goat 40-121) and 29 days (IQR 19-45) in 2008 to 17 days in 2009 farms with more than 200 adult goats and 40 are professional dairy (IQR 12-24 days). sheep farms. In 2005, Q fever was diagnosed for the first time as a cause of abortion at a dairy goat farm, using immunohistochemistry Separate clusters with multiple sources on sections of placenta [5]. A second case was diagnosed later in It is becoming increasingly clear that the overall outbreak 2005. In 2006, 2007 and 2008, six, seven and seven new cases consists of at least 10 separate clusters with multiple sources, at dairy goat farms were confirmed, respectively, mainly in the same mainly in the province of Noord Brabant. For some clusters a clear area where human cases occurred. In the same period, two cases of epidemiological link could be established to small ruminant farms abortion caused by C. burnetii were confirmed at dairy sheep farms, with clinical Q fever cases in animals presented as abortion waves. one in the southern and one in the northern part of the country but For other clusters such a link was less obvious. An example of the these two cases do not seem to be related to human cases. Analyses latter is a medium sized city (87,000 inhabitants) that experienced of abortion outbreaks showed that the average number of goats per a second Q fever outbreak in 2009 similar to the one in 2008. farm was 900 of which 20% aborted, ranging from 10-60%. The In 2008, a dairy goat farm with abortions due to Q fever was average number of sheep on both infected sheep farms was 400 suspected as the source, but in 2009 there were no veterinary and the abortion rate was 5%. notifications from the area. The 73 notified human cases residing in the city were clustered in the same part of the city as the cases Abortion outbreaks before June 2008 were reported on a that were notified in 2008. It remains unclear whether the same voluntary basis to the Animal Health Service and also confirmed source is involved, whether the bacteria have persisted and survived by immunohistochemistry. Since June 2008, notification of Q fever in the local environment, whether the primary source in 2008 in goats and sheep is mandatory in the Netherlands. There is a has resulted in secondary sources in 2009, or whether there is legal requirement for farmers and their private veterinary surgeons increased awareness among health professionals in this part of the to notify the occurrence of abortion in small ruminants held in city based on the 2008 experience. deep litter houses. For large farms (>100 animals) the notification

F i g u r e 1 Q fever notifications by week of notification, 1 January 2007 - 11 May 2009, the Netherlands (2007: n=168, 2008: n=1000, 2009 [week 1-week 19]: n=345)

160

140 probable confirmed

120

o n s i t

a 100 c f i i

80 r o f n t

b e 60 u m N

40

20

0 1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52

2007 2008 2009 Year and week of notification

2 EUROSURVEILLANCE Vol. 14 · Issue 19 · 14 May 2009 · www.eurosurveillance.org criterion is an abortion wave defined as an abortion percentage of 45 kilometer around Uden, a small town in the centre of the higher than 5% among pregnant animals. For smaller holdings, high-risk area. a criterion of three or more abortions in a 30-day period is used. Another, mandatory vaccination campaign led by the Animal Health Service (GD) started on 21 April 2009. From April to From January to April 2009, this new regulation has led to October 2009, 200,000 small ruminants will be vaccinated in an notification of three dairy goat farms with clinical cases of Q area which includes the province of Noord-Brabant and parts of fever. One farm is located in the province of (notified in the provinces of , and Limburg. February), one in the south of the province of Limburg (notified in March), and one in the province of Noord-Brabant (notified in April). Ongoing research Ongoing studies address the factors involved in the 2008 This veterinary notification can potentially facilitate the detection epidemic at a national, regional and local level, the efficacy of the of related human cases or clusters. Veterinarians, physicians and 2008 voluntary vaccination campaign in small ruminants and the the public are informed through targeted mailings, publications nationwide occurrence of C. burnetii antibodies in the community and the media. The exact location of animal farms with clinical Q and in small ruminants. From the human epidemiological fever is now reported to the municipal health service. In February perspective, a case control study is currently underway in the 2009, a nationwide stringent hygiene protocol became mandatory two main affected MHS regions of 2009, ‘Hart voor Brabant’ for all professional dairy goat and sheep farms, independent of Q and Brabant-Southeast. Routinely collected sera of pregnant fever status. women from the affected regions over the period June 2007 to July 2008 are retrospectively screened for Q fever to study the Vaccination campaigns effect of infection on pregnancy outcome (registered in a national In the fall of 2008, a voluntary vaccination campaign was database). An integrated human-veterinary study was started, in implemented in the province of Noord Brabant. In total, about which small ruminant farmers and their animals will be screened 36,000 small ruminants were vaccinated in an area with a radius for presence of C. burnetii antibodies. In addition, environmental samples will be obtained from a subset of these farms and the role of particulate matter in relation to C. burnetii transmission will be further investigated. F i g u r e 2 Conclusion Notified cases of acute Q fever in the Netherlands by three-digit For the third consecutive year the Netherlands is facing a large postal code area, 1 January – 11 May 2009 (n=344*). The black line indicates the mandatory vaccination area covering the province of outbreak of Q fever. The new upsurge in Q fever cases in 2009 Noord Brabant and parts of the provinces of Gelderland, Utrecht, is alarming. The mandatory vaccination campaign among small and Limburg. ruminants that was started in April 2009, if effective, is expected to reduce the occurrence of abortion waves and excretion of Coxiella in the lambing season 2010. There is a large portfolio of ongoing Number of cases multidisciplinary research, but it will take some time before results 1 2-3 become available that eventually will lead to the implementation 4-6 of extended and improved control measures. 7-10 11-20 72

mandatory References vaccination area 1. Maurin M, Raoult D. Q fever. Clin Microbiol Rev. 1999;12(4):518-53. 2. Gageldonk-Lafeber AB van, Koopmans MPG, Bosman A, Heijnen MA. Het vóórkomen van Q-koorts in Nederland [Occurrence of Q fever in the Netherlands]. [Article in Dutch]. Infectieziekten Bulletin. 2003;14(5):173-177. Available from: http://www.rivm.nl/infectieziektenbulletin/bul1405/art_qkoorts.html 3. Schimmer B, Morroy G, Dijkstra F, Schneeberger PM, Weers-Pothoff G, Timen A, et al. Large ongoing Q fever outbreak in the south of the Netherlands, 2008. Euro Surveill. 2008;13(31):pii=18939. Available from: http://www. eurosurveillance.org/ViewArticle.aspx?ArticleId=18939 4. Nabuurs-Franssen MH, Limonard G, Horrevorts AM, Weers-Pothoff G, Besselink R, Wijkmans C, et al. Clinical follow-up after acute Q fever. Scientific Spring Meeting of the Dutch Society for Medical Microbiology and the Dutch Society for Microbiology, 20-22 April, , the Netherlands. International Journal of General and Molecular Microbiology. 2009;95(Supplement 1). 5. Wouda, W, Dercksen D. [Abortion and stillbirth among dairy goats as a consequence of Coxiella burnetii] [Article in Dutch]. Tijdschr Diergeneeskd. 2007;132(23):908-11.

This article was published on 14 May 2009. Citation style for this article: Schimmer B, Dijkstra F, Vellema P, Schneeberger PM, Hackert V, ter Schegget R, Wijkmans C, van Duynhoven Y, van der Hoek W. Sustained intensive transmission of Q fever in the south of the Netherlands, 2009. Euro Surveill. 2009;14(19):pii=19210. Available online: http://www.eurosurveillance.org/ViewArticle. Source: OSIRIS notification system. Map compiled by Ben Bom, Expertise aspx?ArticleId=19210 Centre for Methodology and Information Services, RIVM * For one case the information on postal code is missing

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